Table 2.
Animal models of estrogen receptors in the hypothalamic-pituitary-ovarian axis.
| Models | Estrous cycle | Ovarian cyst | Fertility | Androgen levels | LH levels | Notes | References |
|---|---|---|---|---|---|---|---|
| αERKO mouse | Irregular | YES | Infertile | Androstendione levels↑; testosterone levels↑ | Circulating LH↑; plasma LH levels were significantly lower than ovariectomized wild-type females | Hypoplastic uteri; hyperemic ovaries; E2 levels↑ | (48, 49) |
| αβERKO mice | NA | NA | Infertile | Plasma testosterone levels↑ | Serum LH levels was higher than αERKO females | Normal reproductive tract; no corpora lutea were observed; apparent sex reversal | (48, 50) |
| ENERKI mice | NA | YES | Infertile | Testosterone levels↑ | Serum LH levels↑ | Have hypoplastic uterine tissues; rudimentary mammary gland ductal trees; E2 levels↑ | (51) |
| βERKO | NA | No | Exhibit variable degrees of Subfertility | Plasma testosterone levels↑ | Exhibited wild type-like levels | Aromatase activity↓; estradiol synthesis↓; have normal mammary histology | (53, 55) |
| A neuron-specific ERα mutant mouse | Failed to exhibit estrous cycles | NA | Infertile | NA | Basal LH levels are not elevated | Lack estrogen positive feedback; have dilated, fluid-filled uteri; increased numbers of antral follicles; ack of corpora lutea | (60, 61) |
| neuron-specific ERβ null mice | Normal estrous cycles | NA | Impairment of fertility | NA | Increase in LH secretion after ovariectomy | Normal negative feedback | (61, 70) |
| ERαflox/flox αGSUcre mice | Irregular | NA | Infertile | NA | Basal serum LH levels were not elevated | Maintain a basal level of serum FSH; their ovulatory capacity is comparable to controls; | (64) |
| PitESR1KO | Irregular | YES | Subfertile or infertile | NA | Serum LH levels↑ | A decrease in the number of litters and size of the litters; | (65) |
| PitERtgKO | Irregular | YES | NA | Testosterone levels↑ | Serum LH levels were normal | Pituitary ERα is involved in negative feedback regulation of estrogen; an anomalous sporadic LH secretion profile | (66) |
| GPER KO mouse | Regular | NO | Fertility | NA | Serum LH levels were normal | Normal function of the HPG axis; ovaries developed normally | (69) |
↑ = upregulated; ↓ = downregulated; NA: not available or not assessed. ER, estrogen receptor; GPER, G-protein-coupled estrogen receptor; FSH, follicle stimulating hormone; LH, luteinizing hormone; HPG, hypothalamic-pituitary-gonadal.